Improved survival of patients with melanoma with an antibody response to immunization to a polyvalent melanoma vaccine.

BACKGROUND

Melanoma vaccine treatment appears to slow the progression of melanoma in some patients, particularly in patients in whom it stimulates cellular antimelanoma immune responses. The relationship of vaccine-induced antibody responses to clinical outcome is less clear. The purpose of this study was to investigate the clinical relevance of antibody responses to melanoma vaccine immunization.

METHODS

Eighty-two evaluable patients with surgically resected American Joint Committee on Cancer Stage III malignant melanoma were immunized to a partially purified, polyvalent, melanoma antigen vaccine. Antimelanoma antibodies were measured by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis before vaccine treatment and 1 week after the fourth immunization.

RESULTS

Vaccine treatment induced or augmented antibody responses to melanoma in 32 (39%) of the patients. The antibodies were directed to one or more antigens of 38-43, 75, 110, 150 and/or 210 kDs, which previously have been shown to be expressed preferentially in cultured human melanoma cells. The median disease free survival of patients with a vaccine-induced antibody response to one or more of these antigens was 5.4 years compared with 1.4 years for nonresponders (P = 0.06), and 5-year overall survival was 71% compared with 44%, respectively (P = < 0.01). As determined by Cox multivariate analysis, the difference in overall survival was independent of disease severity or of immunologic competence as evaluated by ability to be sensitized to dinitrochlorobenzene. The difference in survival between antibody responders and nonresponders improved with time.

CONCLUSIONS

The antibody response to vaccine treatment is an immune marker of vaccine activity that appears to be predictive of a later reduction in the recurrence of melanoma and is unrelated to the vaccine's ability to induce cellular immune responses. This finding suggests that vaccine treatment may be effective in slowing the progression of melanoma in some patients and that the protective effect is mediated partly by vaccine-induced antimelanoma antibodies.